IC-processed microneedles

ABSTRACT

A method of fabricating a microstructure is disclosed. The method includes providing a substrate for forming an interface region and an elongated portion extending away from the interface region. A patterned, non-planar etchable structure is formed on one side of the elongated portion of the substrate. An unetchable membrane layer is deposited atop the etchable structure. At least one etching hole is formed in the membrane layer. The etchable structure is etched by placing an etchant into the etching hole to form a cavity underneath the membrane layer, thereby producing a shaft.

This invention was made with Government support under Grant (Contract)No. EEC-8614900 awarded by the National Science Foundation. TheGovernment has certain rights to this invention.

This is a division of application Ser. No. 08/254,328, filed Jun. 6,1994, now U.S. Pat. No. 5,591,139, issued Jan. 7, 1997.

BACKGROUND OF THE INVENTION

The present invention relates generally to microneedles, and moreparticularly to microneedles fabricated by micromachining techniques.

As is well known, needles are used to extract samples of substances fromliving tissue in order to analyze the substances for diagnosticpurposes, or to deliver a drug or a medicine. The majority of needles inuse today are macroneedles, which have a relatively large diameter ascompared to a blood cell and are on the order of millimeters (mm). Thelarge diameter of the macroneedle shaft has the disadvantage of possiblydamaging biological tissue during penetration. Additionally, tissuepenetration by the needle is often painful to the patient because of therelatively large needle diameter.

One type of spring-actuated macroneedle penetrates tissue and dropsblood to a chemical detector for measurement. While this needle may beless painful to the patient because penetration is of a relatively shortduration, the needle is still relatively large and may damage tissue.Additionally, neither of the above-mentioned macroneedles providereal-time blood analysis.

As an alternative to macroneedles, microneedles having a diameter on theorder of micrometers have many applications. For instance, they may beused as precise injection/extraction needles in cell biology, asinjection/extraction heads in a drug delivery system or microchemicalfactory, and as injection/extraction heads in microsurgery. It is alsoadvantageous to have a smaller size needle because the reduced sizedecreases discomfort and pain to the patient. This has been demonstratedin research on electrical microprobes made of silicon for anIC-compatible multichannel neural-recording array. The research hasdemonstrated that silicon microprobes with cross-sections on the orderof tens of micrometers can penetrate living tissue without causingsignificant trauma. (K. Najafi, K. D. Wise and T. Mochizuki, "AHigh-Yield IC-Compatible Multichannel Recording Array," IEEE MicroTrans. on Electron Devices, vol. ED-32, pp. 1206-1211, July 1985.)

Recently, microneedles have been used with an inner diameter ofapproximately 20 micrometers (μm) (1 μm=1 micron=10⁻⁶ m). Thesemicroneedles are formed by heating the end of a glass pipette andlengthening the end until the diameter is reduced to about 20 μm. Mostcells in an animal such as a human measure 10-20 micrometers indiameter. Thus, while these glass microneedles can be used to insert andwithdraw fluids and gasses from a single cell, it is difficult tocontrol the size of the needle shaft during fabrication. Additionally,the resulting needle is not very strong and real-time blood analysis isnot possible. Another disadvantage of glass pipette needles is that itis difficult to incorporate electronics with such needles.

In view of the foregoing, an object of the present invention is toprovide a microneedle having controllable and relatively smalldimensions, including shaft width, and a method for making the same.

Another object of the present invention is to provide a microneedlewhich permits real-time analysis of a fluid being sampled.

Yet another object of the present invention is to provide a microneedlewhich minimizes the amount of trauma to the tissue being penetrated.

Still another object of the present invention is to provide amicroneedle which may be mass produced.

Yet still another object of the present invention is to provide amicroneedle which is strong enough to reliably penetrate biologicaltissue.

A further object of the present invention is to provide a microneedlewhich may incorporate micropumps, microvalves and microdetectors.

Additional objects and advantages of the invention will be set forth inthe description which follows, and in part will be obvious from thedescription, or may be learned by practice of the invention. The objectsand advantages of the invention may be realized and obtained by means ofthe instrumentalities and combinations particularly pointed out in theclaims.

SUMMARY OF THE INVENTION

The present invention is directed to an IC-processed microneedle formedfrom a substrate which defines an interface region and an elongatedportion extending away from the interface region. A shaft is formed fromthe elongated region by a shell, which defines an enclosed channelwithin the shaft. One end of the shaft is attached to the interfaceregion. The shaft includes ports which permit fluid to flow through themicroneedle.

The method of the present invention includes a sequence of steps forforming an IC-processed microneedle. First, a substrate is provided forforming an interface region and an elongated portion extending away fromthe interface region. A patterned non-planar etchable structure is thenformed on the frontside of the elongated portion of the substrate. Anunetchable membrane layer is deposited atop the etchable structure, andetching holes are opened in the membrane layer. One of the etching holesis at an end of the membrane layer and a second etching hole ispositioned at a second end of the membrane layer. Next, the etchablestructure is etched to a predetermined extent to form a cavityunderneath the membrane layer, thereby producing a shaft formed from themembrane layer and the elongated portion of said substrate.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of the specification, schematically illustrate a preferredembodiment of the invention and, together with the general descriptiongiven above and the detailed description of the preferred embodimentgiven below, serve to explain the principles of the invention.

FIG. 1A is a perspective view of an embodiment of a silicon processedmicroneedle.

FIG. 1B is a cross-sectional view of the microneedle as taken along line1B--1B of FIG. 1A.

FIG. 1C is a cross-sectional view of the microneedle as taken along line1C--1C of FIG. 1A.

FIG. 2A is a plan view of the microneedle prior to detachment from thesubstrate.

FIG. 2B is a cross-sectional view of the microneedle as taken along line2B--2B of FIG. 2A.

FIGS. 3A-1 to 3N-2 schematically illustrate a microneedle fabricationprocess according to the present invention. The left-hand figures aretaken along line 3L--3L of FIG. 1A, and the right-hand figures are takenalong line 3R--3R.

FIGS. 4A and 4B are views illustrating a microheater and its positioningrelative to the microchannel, respectively.

FIGS. 5A-5E show the sequence of steps in fabricating the microneedlewith on-chip CMOS (complementary metal-oxide semiconductor) as takenalong line 5--5 of FIG. 1A.

FIG. 6 is a schematic diagram showing the microneedle penetrating tissuein a first application of the present invention.

FIG. 7 is a schematic diagram including a detailed portion showing themicroneedle penetrating tissue in another application of microneedleuse.

FIGS. 8A and 8B show alternative embodiments of the microneedle.

DESCRIPTION OF THE PREFERRED EMBODIMENT

The present invention will be described in terms of the preferredembodiment. The preferred embodiment is an apparatus and method forfabricating IC-processed microneedles. Referring in detail to thedrawings, wherein like reference numerals designate like parts inseveral figures, and initially to FIG. 1A, a microneedle 10 inaccordance with the present invention is illustrated.

Microneedle 10 includes an interface region 11 and a shaft 14 having amicroflow channel 78 therein along its length. A distal end 20 of shaft14 can be inserted into tissue (not shown) so that liquids (includinggases) may be delivered to or taken from a patient, for example, via adistal fluid port 18. A shank fluid port 22 is located on shank orproximal end 12 of shaft 14 to deliver or receive fluids. Themicroneedle may include more than two ports, as desired. Microflowchannel 78 runs along the length of fully-enclosed microneedle shaft 14.A series of thin polysilicon heating resistors 60 are located oninterface region 11 along the floor of microflow channel 78. Interfaceregion 11 is sufficiently thick to permit incorporation of on-chipelectronics 24 for real-time fluid analysis. Heating resistors 60 may beused to form a thermally-driven, cascaded-bubble micropump or simpleheater. The microneedle may also include detector resistors 62 whichextend along the bottom of the microchannel (see FIG. 1B) and arecoupled to electrodes 84 (FIG. 3L-2) on the tip 86 of the needle.Microflow channel 78 is formed by removing sacrificial layers fromunderneath a shell 26 during processing. In order to access thesacrificial layer, etch access holes 74 are opened and then filled afteretching. The fabrication procedures will be discussed below in relationto FIGS. 3A-1 through 3N-2.

FIG. 1B shows a cross-section of fully-enclosed microflow channel 78.The channel height is approximately 9 μm, and is indicated by dimension"G", and the channel width "H" may be between 30 μm to 60 μm. The needleheight "I" is about 70 μm, and the needle width "J" is approximately 80μm at the tip region.

FIG. 1C illustrates the positioning of a polysilicon resistor 60 oninterface region 11. Contact pads 36 are situated on both sides of themicroflow channel 78 at shank end 12 and provide an outside connectionto resistors 60, which function as microheaters. Note that detectorresistors 62 cannot be seen in FIG. 1C because this cross-section istaken along line 1C--1C on the interface region. The detector resistorsextend along the length of the channel but do not extend into theinterface region any further than is necessary to couple them toelectronics 24. The location of both resistors can be best seen in FIG.3N-2.

FIG. 2A is a plan view of a microneedle 10 before it is separated fromwafer or substrate 46 by breaking beams 44. Support beams 44 connectmicroneedle 10 to substrate 46 and facilitate testing and manipulationof the microneedle prior to its final use. Although only a singlemicroneedle 10 is shown, many microneedles may be fabricated on a singlewafer. Area 40 marks the area where microneedle 10 will be separatedfrom substrate or thin-film 46. Interface region 11 may be used as anintegrated-circuit (IC) interface region of approximately 2 to 3millimeters (mm)². The tip region 86 is formed at an angle θ ofapproximately 45° to the plane of the needle shaft 14, to form a sharptriangular tip 87. The width of the interface region, indicated bydimension "X", is approximately 1.5 mm, and the length of the shaft,indicated by dimension "Y", is between 1 and 6 mm. At shank end 12,interface region 11 widens out to a large surface area, suitable forincorporation of additional integrated electronic and/or fluidicdevices.

Cross-sectional dimensions of a completed microneedle 10 are shown inFIG. 2B after if has been detached from wafer 46. Wafer 46 has aninitial thickness of between 500 and 550 μm, as indicated by "Z". Thewafer thickness of the microneedle is reduced during fabrication. Shaft14 has a thickness of approximately 50 μm indicated by dimension "I". Inmicroneedles which are 3 mm-long or longer, microneedle 10 tapers fromthe tip end 86, where it is approximately 80 μm wide, to 140 μm, whereit joins the shank in order to increase strength. The retainedsingle-crystal silicon layer 46 provides a rigid spine which addsstrength to the needle. Note that there is no single-crystal silicon atthe tip region 86, so that the tip is sharper and smaller than theportion of the shaft including single-crystal silicon.

The fabrication sequence for formation of a microneedle is shown inFIGS. 3A-1 to 3N-2. Seven masks may be used. The drawings are not toscale, and dimensions should be taken from the text; the drawings are toillustrate the process, and not necessarily the preferred dimensions ofthe microneedle. The microneedle is formed using IC (integrated circuit)processing methods, e.g. oxidation, lithography, chemical vapordeposition, doping, and etching. Briefly, microchannel 78 issurface-micromachined onto a single-crystal silicon substrate orthin-film 46 that is mostly etched from the wafer backside along shaft14 in the final fabrication step. While only a single microneedle isshown in the following steps, it will be understood that manymicroneedles may be fabricated simultaneously on a single wafer.

FIGS. 3A-1 AND 3A-2 show a <100>-oriented lightly doped n-type siliconwafer 46 which is 500-550 μm thick. A thick masking layer 47 of silicondioxide (SiO₂) 1.2 μm thick is thermally grown on wafer frontside 48 andbackside 50. Masking layer 47 is patterned as shown, and boron isdiffused at approximately 1125° C. for fifteen hours to form a 12μm-deep heavily doped p-type region 52. Both the future interface region11 and shaft 14 are indicated generally in these figures. Boron-dopedregion 52 defines tip region 84 (FIG. 2A), extends along the needleshaft and defines the perimeter of interface region 11, as best shown inFIG. 2A. Boron-doped region 52 acts as an etchant stop since EDP(ethyleneidamine pyrocatacol and water), used during fabrication, doesnot etch boron-doped silicon. Note that the boron-doped region isomitted from the center of IC interface region 11 because, as wellknown, any electronic components incorporated into the microneedle mustbe atop undoped silicon.

Masking layer 47 is then removed, and a 400 nanometer (nm) thick layer54 of SiO₂ is thermally grown on the wafer. A 600 nm low-stress nitridelayer 56 is then deposited by low pressure chemical vapor deposition(LPCVD) for passivation. As well known, CVD will deposit on all exposedsurfaces of the wafer. Silicon dioxide layer 54 will serve as a thermalbarrier underneath the microheater as well as an electronic insulationlayer. Silicon nitride layer 56 serves as the bottom layer of themicrochannel. Next, a 600 nm-thick LPCVD phosphorus-dopedpolycrystalline silicon layer 58 is then deposited, and the resultingstructure is as shown in FIGS. 3B-1 and 3B-2.

Polysilicon layer 58 is patterned and etched to define polysiliconheating resistors 60 on interface region 11 (FIG. 3C-1) and, if desired,polysilicon detector resistors 62 (FIG. 3C-2). Note thatphosphorus-doped polycrystalline silicon layer 58 is also etched away onbackside 50. Resistors 60 are shown perpendicular to the length ofchannel 78; however, they may also be fabricated such that they extendlengthwise parallel to channel 78 or in any other orientation under thearea of fluid flow. Resistors 60 are approximately 50 μm long. Detectorresistors 62 extend lengthwise along shaft 14 and function as wires torelay a signal from electrodes or recording sites 84 (FIG. 2A) to theshank end of the channel, where electronics 24 process the signals.There is one resistor for each electrode and so the width of channel 78determines the number of electrodes which may be fabricated within thechannel. The microneedle shown has two resistors, but more electrodescould be incorporated into the microneedle by widening the channel oraltering the aspect ratio of the resistors. Both heating resistors 60and detector resistors 62 are approximately 0.5 μm high, and 2 μm wide.Heating resistors 60 are approximately 50 μm long. The length ofdetector resistors 62 depends upon the eventual length of shaft 14.However, resistors 62 should reach the tip of the needle so thatelectrodes or recording sites may also be at the needle tip 86.

Referring now to FIGS. 3D-1 and 3D-2, a thin layer 64 of approximately150 nm of LPCVD low-stress nitride is deposited to cover and protectpolysilicon resistors 60 and 62 during subsequent EDP (ethyleneidaminepyrocatacol and water) etching. A layer 66 of 5 μm phosphosilicate glass(PSG) is deposited by LPCVD process and then an approximately 3 μm layer68 of a low-temperature oxide (LTO) such as undoped LPCVD SiO₂ isdeposited. The LTO layer on top of the PSG gives better adhesion tophotoresist. The LTO layer also desirably minimizes hydrofluoric acid(HF) attack on the interface between the photoresist and PSG.Furthermore, no high-temperature densification process is needed so thatthe future circuitry in the IC interface region 11 will not be damaged.

The microflow channel is then patterned and wet-etched in a 5:1 solutionof buffered HF, as shown in FIGS. 3E-1 AND 3E-2. The buffered HF etchesboth PSG 66 and LTO 68 layers as shown. The primary configuration of thechannel is formed by this etch. A 0.5 μm LTO layer 71 (FIGS. 3F-1 and3F-2) is then deposited by LPCVD to provide an area for future etchaccess holes. The resulting shell formed from LTO layers 68 and 71 isapproximately 3-4 μm. LTO layer 71 is then patterned and wet-etched in5:1 BHF (buffered hydrofluoric acid) to provide an etch channels area 70as shown in FIG. 3F-1. Dry-etching is also possible for this step. LTOlayer 71 is also deposited on backside 50, but is not shown because theyit is removed after the BHF wet-etch. The etch channels area 70 isadvantageously only about 0.5 μm thick because it will be relativelyeasy to fill etch holes later in the fabrication process, as will becomeapparent below.

The wafer is then coated with a 1 μm thick layer 72 of LPCVD low-stresssilicon nitride which will become a portion of the microchannel shell 26(FIG. 1B). Etch access holes 74 and distal 18 and shank 22 fluid portsare defined and etched in a plasma etcher through silicon nitride layer72. The etch access holes lead to the sacrificial PSG and LTO layerswhich will be etched. The cross-section appears as in FIG. 3G-1; theetch access holes are not visible in FIG. 3G-2. Etch access holes areformed along the length of the shaft 14 in etch channel area 70, and arelocated every 25 μm. The duration of the sacrificial-layer etching stepis thus independent of channel length. The etch access holes areapproximately 5 μm×5 μm.

Fluid ports 18 and 22 will permit flow of a liquid through themicrochannel 78 when the needle is fully operational. The fluid portsare approximately 20 μm×20 μm. In a preferred embodiment, distal fluidport 18 is positioned 150 μm up the microneedle from the tip 86. Sincethe PSG and LTO layers are underneath nitride layer 72, resistors 60 and62 will not be affected by this etch. Additionally, because the fluidports are relatively large as compared to the etch access holes, thefluid ports will not be completely filled during deposition of siliconnitride sealing layer 76, in which etch access holes are sealed(described below). As an alternative, the fluid ports may be etchedafter the sacrificial PSG and LTO layers are removed from within themicrochannel if good process control is employed. However, this methodhas the possible drawback of affecting silicon nitride 64, whichprotects resistors 60 and 62. Since layer 64 is approximately 150 nm,the resistors will not be affected because the etch will remove about 50nm of layer 64. As another alternative, resistors 60 and 62 may belocated so that they will not be underneath the fluid ports.

After the etch access holes and fluid ports have been formed, the waferis immersed in concentrated hydrofluoric acid (48% HF) for approximately2.5 minutes to remove PSG layer 66, and LTO layers 68 and 71 underneathnitride shell 72. Wafer 46 is then rinsed in de-ionized water, and anyresidual oxide is removed from the silicon nitride 72 using HF. Theresulting microneedle is then as shown in FIGS. 3H-1 and 3H-2.

All etch access holes 74 are sealed by deposition of an additional 1.5μm thick layer 76 of LPCVD low-stress nitride to form a shell 26, asshown in FIGS. 3I-1 and 3I-2. Since the thickness of the PSG beforeetching was only about 0.5 μm underneath the etch access holes 74, a 1.5μm deposition of silicon nitride insures that the hole will becompletely filled. Microchannel 78 is thus completely sealed, except forthe fluid ports. Fluid ports 18 and 22 are sufficiently wide that theywill not be sealed by deposition of the 1.5 μm silicon nitride sealinglayer. The size of the fluid ports is somewhat reduced during this step,but they remain sufficiently large enough to permit adequate fluid flow.A thin layer 76 of silicon nitride is also deposited in channel 78, asshown.

It is possible to form channel 78 without including etch access holes 74by using the fluid ports to remove the sacrificial PSG and LTO layers.However, this approach would require more time to fully evacuate thechannel. A clear advantage would be that the previous sealing step couldbe omitted.

The needle has now been substantially fabricated, and steps to separateit from the wafer are now taken. EDP etch pre-openings or windows 80 arepatterned by a mask and plasma etched in order to facilitate finalseparation of microneedle 10 from the rest of the wafer, as shown inFIGS. 3J-1 and 3J-2. Etch windows 80 are stopped at the 400 nm-thickSiO₂ layer 54. The etch windows will facilitate removal of themicroneedle from the wafer during subsequent backside etch. It will bedesirable later to remove both layers 54 and 56 in order to separate themicroneedle. However, the etch is stopped at layer 54 at this pointbecause it is relatively easy to etch silicon dioxide and relativelydifficult to etch silicon nitride. Thus, silicon nitride layer 56 isremoved from the frontside prior to backside etching.

Next, an electrode hole 82 is formed by patterning and plasma-etchingdown to the 600 nm-thick phosphorus-doped polycrystalline silicon layer58 to permit electrical contact with resistors 62. Only a singleelectrode hole 82 is shown in FIG. 3K-2 (the electrode is not visible inFIG. 3K-1), but the process for fabricating contact pads 36 (see FIG.1C) is identical and is performed at the same time as electrodefabrication. The electrodes function as recording sites at distal end 20and permit monitoring of biological electrical activity, as will bediscussed below. The contact pads permit coupling of electronics withheating resistors 62. After electrode hole 82 is formed, a thin layer oftitanium is deposited, followed by a thicker layer of platinum whichcompletely fills the hole, forming a complete electrode 84 as shown inFIG. 3L-1. Again, the electrode is not visible in FIG. 3L-2.

At this point, microneedle 10 is essentially complete and must now bepartially separated from wafer 46. The backside of the wafer ispatterned with a blank mask and without alignment to open the etchingareas of individual die to free the microneedles from the waferbackside. In a preferred fabrication method, the mask is positioned sothat the microneedle tip extends to the blank center of the mask. Shankend 12 is covered by the mask and is not etched, but distal end 18 isnot covered by the mask and so end 18 is completely etched. A timed EDPetch reduces the silicon wafer thickness to 120 μm, as shown in FIGS.3M-1 and 3M-2. After rinsing in de-ionized water, the wafer is immersedin a 5:1 BHF solution which attacks only the pre-opened, bare SiO₂ layer54. Pre-EDP etch window 80 is thus deepened so that it extends toundoped silicon layer 46.

Immersion in an EDP timed etch reduces the 120 μm thickness to 50 μm atshank end 12 as shown in FIGS. 3N-1 and 3N-2. As also shown in FIG. 2B,tip region 86 of shaft 14 does not contain any single-crystal silicondue to the corner-etching behavior of EDP. A combination of corneretching and etching from the crystal backside also removes the thickernon-doped single-crystal silicon for approximately 50 μm along theneedle underside from the tip end. The corner etching behavior of EDP isaddressed by B. Bassous in "Fabrication of Novel Three-DimensionalMicrostructures by the Anisotropic Etching of (100) and (110) Silicon,",IEEE Trans. on Electron Devices, Vol. Ed-25, No. 10, Oct. 1978.

The microneedle is then partially separated from the wafer, and remainsattached through support beams 44, best shown in FIG. 2A. Since the manymicroneedles fabricated on wafer remain attached to the wafer, it iseasier to package, transport, and handle the needles than if they werefully freed by the anisotropic etch. When a free-standing microneedle isdesired, the microneedle is simply detached from the rest of the waferby using, for example, tweezers or some other similar implement to applypressure to beams 44. When the beams are broken, the microneedle isfreed from the wafer.

FIG. 4A shows a simplified view of resistor 60 and contact pads 36 (alsoFIG. 1C) of microneedle 10 (not shown). As explained above, the contactpads and resistor are defined on a single-doped polysilicon layer. Asilicon dioxide layer 54 separates silicon substrate 46 and the contactpads and resistor. Resistor 60 functions as a microheater when a voltagesource 30 supplies current to contact pads 36. The resistors propel aliquid to distal fluid port 18, as explained below. FIG. 4B illustratesthe positioning of microneedle shell 26 above resistors 60. As notedabove, since there is a silicon dioxide layer 54 underneath thepolysilicon heater, heat conduction from the heater to silicon substrate46 is restricted because SiO₂ layer 54 acts as an insulator. Due to thelow power dissipated in the heater, the temperature of undoped siliconsubstrate 46 remains at the ambient temperature. The heaters areespecially advantageous if a chemical reaction occurs quickly inresponse to heat. The reaction may occur in the microneedle and then maybe quickly delivered to the appropriate tissue.

A single resistor is shown in FIGS. 4A and 4B to illustrate itspositioning. However, in a preferred embodiment five resistors 60 form athermally-driven cascaded bubble pump (FIG. 2A). In operation, theresistor furthest from the needle tip is heated and produces a singlevapor bubble. Then, the adjacent resistor is heated and the bubble ismoved sequentially down the line of resistors toward the distal end ofthe needle shaft. The resistors are heated quickly and sequentially, sothat precise fluid control is possible. If a cascaded bubble pump is notemployed, a fluid may move down the needle shaft simply by means ofgravity.

In addition to resistors, micropumps and microvalves (neither is shown)may be incorporated onto the microneedle. For example, the resistors mayalso be part of a bubble-powered micropump coupled to an actuator. Asdiscussed above, the bubble generation system creates individual,spherical vapor bubbles from 2 to 500 μm in diameter by locally heatinga fluid with a thin film resistor. Prior research has shown thatmicrobubbles are capable of actuating a polycrystalline siliconcantilever (See L. Lin and A. P. Pisano, "Bubble Forming on a Micro LineHeater", Proceedings of ASME Winter Annual Meeting, MicromechanicalSensors, Actuators and Systems, DSC-Vol. 32, pp. 147-163, 1991). Othermicropumps can also be employed with these microneedles, such as thoseactuated by ultrasonic Lamb waves (See R. M. Moroney, R. M. White and R.T. Howe, "Microtransport Induced by Ultrasonic Lamb Waves," AppliedPhysics letters, pp. 774-776, V59, August, 1991); piezoelectrics (See H.T. G. Van Lintel, F. C. M. Van Deol and S. Bouwstra, "A PiezoelectricMicropump Based on Micromachining of Silicon," Sensors and Actuators,Vol. 15, pp. 153-157, 1988, and M. Esashi, S. Shoji and A. Nakano,"Normally Closed Microvalve and Micropump Fabricated on a SiliconWafer," Sensors and Actuators, Vol. 20, pp. 163-169, Nov. 1989); andelectrohydrodynamics (See S. F. Bart, L. S. Tavrow, M. Mehregany and J.H. Lang, "Microfabricated Electrohydrodynamic Pumps," Sensors andActuators, Vol. 21, N1-3, pp. 193-197, Feb. 1990).

FIGS. 5A-5E briefly illustrate a process for fabricating a microneedlewith on-chip CMOS (complementary metal-oxide semiconductor) devices.Both CMOS and BiCMOS are compatible with the microneedle fabricationprocess. The manufacturability of an on-chip electronic interface withthe microneedle is essential for a broad range of applications. Themanufacturabilities of the on-chip CMOS and bipolar CMOS devices withthe IC-processed microneedle increase the signal conditioning ability,which is not a possible feature in needles fabricated by other means.

Formation of the microneedle itself is via the same steps illustrated inFIGS. 3A-1 to 3N-2, and the CMOS devices are fabricated using standardprocesses. FIGS. 5A-5E, illustrate the best mode sequence forintegrating fabrication of both the microneedle and CMOS devices. FIGS.5A-5E are taken along line 5--5 of FIG. 1A, although no CMOS devices areshown in FIG. 1A. FIG. 5A is a cross-sectional view of the partiallyconstructed needle shaft 14 and the interface region 11. The heavilydoped p-type region 52 has been formed and silicon dioxide 54 andsilicon nitride 56 layers have been deposited on wafer 46, as explainedin connection with FIG. 3B-1. Next, silicon dioxide 54 and siliconnitride 56 layers are removed from interface region 11, where the CMOSdevices will be fabricated. CMOS fabrication then commences usingstandard processes, and a p-type well 90, p-type layer 92, thick SiO₂layer 94, and n-type layer 96 are formed by known methods. Polysiliconlayer 58 (see FIG. 3B-1) is then deposited and polysilicon gates 98 aredefined with the same masking operation which defines polysiliconresistors 62 (see FIG. 3C-1). The resulting structure is as shown inFIG. 5B.

FIG. 5C shows PSG layer 66 and LTO layers 70 and 71, as in FIG. 3F-1.Etch access holes 74 are formed and the PSG and LTO layers are etched toform microchannel 78, as explained in conjunction with FIG. 3H-1. EDPetch pre-openings or windows 80 are formed as explained in connectionwith FIG. 3J-1, and the resulting structure is shown in FIG. 5D. Duringthese operations, interface region 11 is masked so that the CMOS deviceswill not be affected.

Next, CMOS device fabrication is completed when metal contacts 99 areformed which connect to p-type 92 and n-type 96 regions, as well knownin the art. The resulting structure is as shown in FIG. SE. Themicroneedle is then separated from the rest of the wafer, as explainedin connection with FIGS. 3K-1 to 3L-2.

The microneedle of the present invention can be expected to have broadapplications to fluid sampling, fluid delivery, and precisely locatedchemical-reaction stimulation. Microneedle 10 has successfullypenetrated tissue without damage to the needle, due in part to thestrong silicon backbone along the needle shaft. Since the microneedleshave a thickness of approximately 70 μm (microchannel height, boronregion plus single crystal region) over most of their length, they arerelatively strong. Another advantage of the design of the microneedle isthat during and after processing it is surrounded by regions of siliconhaving full wafer thickness, providing even greater strength, easy postprocessing and handling.

An application of the microneedle of the present invention isillustrated in FIG. 6, which shows a real-time blood analysis system.Tip 86 of microneedle 10 is inserted through tissue 100 into a bloodvessel 102. As blood is drawn into the needle via shaft 14, the blood isanalyzed by an on-chip blood analysis amplifier and A/D converter 104,which converts an analog signal to a digital signal for digital output106. Digital output 106 is transmitted to a computer 108 for real-timecomputer analysis, and displayed, for example, on a cathode-ray tube.Since the diameter of shaft 14 is only approximately 50 μm, it causesminimal pain to the patient during penetration because there is littletrauma to the tissue involved. Another possible application of thesilicon-processed microneedle is administration of drugs on a long termbasis. For instance, the microneedle may be implanted in a small tumorand used to administer small, concentrated doses of a drug on anextremely local level.

Another application of the microneedle is shown in FIG. 7, in which themicroneedle is used for recording neural signals. Specifically,microneedle 10 is inserted into neural tissue 110 such that tip region86 is between adjacent cells 112. As a chemical substance 114 isdelivered to neural tissue 110, recording sites or electrodes 84 on tip86 detect the neural response to substance 114. The recording sitespassively detect a signal which is relayed to an amplifier 104, asdiscussed above. Since microneedle 10 is so small, the damage caused bypenetrating brain tissue is reduced. Additionally, recording orelectrode sites 84 provide the ability to obtain real-time neuralmeasurements. Alternatively, recording sites 84 may be used to measureneural activities or to apply an electric field, current, charge orvoltage to the tissue. Processing electronics may be located separatefrom the interface region, as desired. Additionally, an active devicemay be positioned at the tip of the microneedle to process a detectedsignal.

FIGS. 8A and 8B show alternative embodiments of a microneedle 120. Themicroneedle may include two or more microchannels 122 and 124 so thattwo different fluids may be delivered via the shaft 14. Microchannels122 and 124 are formed on separate portions of a substrate, and there isno substrate between them. Additionally, electrodes 84 may be fabricatedat the end of each channel to detect tissue response to chemicaldelivery. Electronics 24 may be fabricated as necessary depending uponthe number of channels, electrodes, etc. As shown in FIG. 8B, shank end12 may also include a network of channels 126 for distributing a fluidfor analysis. Alternatively, if a number of fluids must be mixed justbefore delivery, it is possible to have them mix in channels 122 and124.

In summary, an apparatus and method for a IC-processed microneedle havebeen described. Microneedle 10 has on-board resistive heaters 60 forbubble-pumping elements, fluid ports 18 for liquid/gas transport, andIC-interface region that can be used for future on-chip circuitry andmicrofluidic components. The process for producing the needles isadvantageous because the needles are surrounded by regions of siliconhaving full wafer thickness. This feature simplifies post-processing,handling, and lead attachment which can be accomplished prior to freeingthe microneedle by breaking support beams. The mask fabrication processis compatible with IC processes. The microneedles are sufficientlysturdy to penetrate tissue without being damaged and without significantpain to the patient. Since the microneedle may be batch fabricated, theresulting microneedle is relatively inexpensive to produce as comparedto a macroneedle. The size of the shaft diameter may be readilycontrolled using known semiconductor fabrication techniques.

The present invention has been described in terms of a preferredembodiment. The invention, however, is not limited to the embodimentdepicted and described. Rather, the scope of the invention is defined bythe appended claims.

What is claimed is:
 1. A method of fabricating a microstructure,comprising the steps of:providing a substrate for forming an interfaceregion and an elongated portion extending away from said interfaceregion, said substrate including a frontside and a backside; forming apatterned, non-planar etchable structure on the frontside of saidelongated portion; depositing an unetchable membrane layer atop saidetchable structure; opening at least one etching hole in said membranelayer; and etching said etchable structure by placing an etchant intosaid etching hole, said etchable structure being etched to form a cavityunderneath said membrane layer, thereby producing a shaft formed fromsaid membrane layer and said elongated portion of said substrate.
 2. Themethod of claim 1 further including the step of:depositing additionalmembrane material to close said etching hole.
 3. The method of claim 1wherein said opening step includes opening a plurality of etching holesincluding a first etching hole at a first end of said membrane layer anda second etching hole at a second end of said membrane layer.
 4. Themethod of claim 3 further including:depositing additional membranematerial to close said plurality of etching holes except said first andsecond etching holes, which form ports for permitting flow of a liquidtherethrough.
 5. The method of claim 1 further including the stepof:prior to said step of forming said patterned non-planar etchablestructure, forming at least one polysilicon resistor, such that saidpatterned non-planar etchable structure is then deposited atop saidresistor.
 6. The method of claim 1 further including the stepsof:patterning the backside of said substrate; and etching the backsidein order to separate said shaft and said interface region from saidsubstrate.
 7. The method of claim 6 wherein said backside etching stepfurther includes the steps of:etching the backside such that saidinterface region and said elongated portion remain attached to saidsubstrate; etching portions of thin films on the frontside of saidsubstrate to form an opening through to said substrate; and etching saidsubstrate such that said opening extends through said substrate on saidelongated portion, said elongated portion being detached from saidsubstrate.
 8. A method of fabricating a microneedle, comprising thesteps of:providing a semiconductor substrate for forming an interfaceregion and an elongated portion; forming a shaft enclosing amicrochannel along said elongated portion, said shaft extending fromsaid interface region; and forming first and second ports through saidshaft for permitting transport of a liquid through said microchannel. 9.The method of claim 8 further including the step of:providing a firstresistor on said substrate within said shaft for heating a liquid whichflows therethrough.
 10. The method of claim 9 further including the stepof:fabricating a CMOS device on said interface region.
 11. The method ofclaim 10 wherein said CMOS fabricating step includes depositing apolysilicon layer, said polysilicon layer also forming said firstresistor.
 12. A method of fabricating a microstructure, comprising thesteps of:providing a substrate for forming a region and an elongatedportion extending away from said region, said substrate including afirst side and a second side; forming a patterned etchable structure onsaid first side; depositing an unetchable layer atop said etchablestructure; opening at least one etching hole in said unetchable layer;and etching said etchable structure by placing an etchant into said atleast one etching hole, said etchable structure being etched to form acavity underneath said unetachable layer, thereby producing a shaftformed from said unetchable layer and said elongated portion of saidsubstrate.